There are two primary objectives of the proposed research: first, to better understand the mode of action of the diabetogenic agents alloxan and streptozotocin and second to attempt to understand the interrelationships between the pharmacology of catecholamine neurotransmission and carbohydrate metabolism. The first objective will be to pursue the premise that the hydroxyl radical is the causative species in alloxan induced diabetes and to determine if this indeed is the case. The major experimental rationale will be to see if the previously published positive correlation between the capacity to prevent alloxan-induced diabetes and the capacity to react with the hydroxyl radical continues with a larger number of compounds. Similar comparative studies will be done with streptozotocin. The second primary objective will be to try to understand why there is a diminished response to amphetamine in an alloxan-diabetic animal. Experiments will be done with other diabetic animals (streptozotocin diabetic and genetically diabetic) and other CNS stimulants (e.g., nomifensine, mazindol) to attempt to see if the above phenomenon, namely the diminished amphetamine effect in alloxan diabetic animals, is perhaps more general. After these experiments are done, experiments based on well-documented neuropharmacological methodology (e.g., catecholamine uptake, catecholamine release, catecholamine levels) will be performed. Hopefully the results will lead to a better understanding of both experimental diabetes and catecholamine-carbohydrate interrelationships.